Cancer is a ubiquitous disease of unregulated cell proliferation that can lead to tumor formation and systemic metastatic seeding of cancerous growth at new physical sites. In all cancers, the targeting of microtubule spindle assembly has been shown to be an effective anti-proliferative therapy and enhances patient survival giving rise to perhaps the most potent class of anti-cancer therapeutic drugs available: those that lead to genomic instability and growth arrest by targeting the mitotic spindle, which is crucial for genetic fidelity during cell division. Mitotic spindle protein (MSP) drugs that have been developed for cancers include those that target the dynamic behavior of the microtubules (such as paclitaxel) or the bipolar organization of microtubules such as blocking microtubule binding of the Kinesin-5 motor domain (for example, Ispinisib or Monastrol.)
Anti-MSPs are proven, powerful anti-cancer reagents, yet the current portfolio of MSP drugs approved or in the pipeline is insufficient in terms of the structural and functional complexity of the mitotic spindle. What is needed, therefore, are agents with the ability to act upstream of other anti-MSP cancer therapies, which would eliminate cancer cell access to typical mitotic recovery mechanisms and reduce or block drug resistant lines from developing, either alone or in combination with other anti-MSPs.